Immunogenicity of COVID-19 Vaccination in Patients With End-Stage Renal Disease Undergoing Maintenance Hemodialysis: The Efficacy of a Mix-and-Match Strategy

BackgroundThe objective of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19) vaccination in patients with end-stage renal disease (ESRD) on hemodialysis.MethodsESRD patients at the hemodialysis center of a tertiary-care university-affiliated hospital and healthy employees at the clinical laboratory center were prospectively recruited between March and June 2021. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody analysis, blood samples were collected serially on days 0, 14, 28, and 56 after the first vaccine dose, and on days 7 and 50 after the second dose. Antibodies against the SARS-CoV-2 spike protein were quantified, and SARS-CoV-2 neutralizing antibodies were measured in the serum and plasma.ResultsThirty-one ESRD patients and 55 healthy employees were regularly monitored. Twenty-five (80.6%) ESRD patients on hemodialysis received a mix-and-match strategy with ChAdOx1-BNT162b2 (AZ–Pf group) and six (19.4%) received two doses of ChAdOx1 (AZ–AZ group). ESRD patients on hemodialysis showed lower binding antibody titers and neutralizing antibody activities compared to healthy participants following the first vaccination with ChAdOx1. After the second dose, AZ-Pf group had higher immunogenicity than healthy people on days 7 and 50. The binding antibody titer and neutralizing antibody activities on days 7 and 50 were significantly higher in the AZ–Pf group than in the AZ–AZ group.ConclusionESRD patients on hemodialysis receiving the mix-and-match strategy (ChAdOx1–BNT162b2) have COVID-19 vaccine immunogenicity comparable to healthy individuals receiving two doses of ChAdOx1.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT04871945","term_id":"NCT04871945"}}NCT04871945     

Microstructural Characterization of Additively Manufactured Metal Components Using Linear and Nonlinear Ultrasonic Techniques

Metal additive manufacturing (AM) is an innovative manufacturing technology that uses a high-power laser for the layer-by-layer production of metal components. Despite many achievements in the field of AM, few studies have focused on the nondestructive characterization of microstructures, such as grain size and porosity. In this study, various microstructures of additively manufactured metal components were characterized non-destructively using linear/nonlinear ultrasonic techniques. The contributions of this study are as follows: (1) presenting correlation analyses of various microstructures (grain size and texture, lack of fusion, and porosity) and ultrasonic properties (ultrasonic velocity, attenuation, and nonlinearity parameters), (2) development of nondestructive microstructural characterization techniques for additively manufactured components; and (3) exploring the potential for the online monitoring of AM processes owing to the nondestructive nature of the proposed technique. The performance of the proposed technique was validated using additively manufactured samples under varying laser beam speed conditions. The characteristics of the target microstructures characterized using the proposed technique were consistent with the results obtained using destructive optical microscopy and electron back-scattered diffraction methods.     

GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles—continuous outcomes

Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of the outcome measure are not easily interpretable, choosing a threshold to create a binary outcome and presenting relative and absolute effects become a more attractive alternative.When studies use different measures of the same construct, calculating summary measures requires converting to the same units of measurement for each study. The longest standing and most widely used approach is to divide the difference in means in each study by its standard deviation and present pooled results in standard deviation units (standardized mean difference). Disadvantages of this approach include vulnerability to varying degrees of heterogeneity in the underlying populations and difficulties in interpretation. Alternatives include presenting results in the units of the most popular or interpretable measure, converting to dichotomous measures and presenting relative and absolute effects, presenting the ratio of the means of intervention and control groups, and presenting the results in minimally important difference units. We outline the merits and limitations of each alternative and provide guidance for meta-analysts and guideline developers.     

Determinants of Birthweight; Gender Based Analysis

The objective of this cross sectional study is to look at determinants of birth weight and their association with the gender of the baby in 2,795 full term children living in the occupied Palestinian territory, derived from a stratified random sample of 2,994 households in the West Bank and 2,234 households in the Gaza Strip. The response rate was 85%. Multivariable analysis using analysis of variance for mixed models showed that sex and birth order, maternal age and education and to a lesser extent region were determinants of birth weight for all children. The effect of maternal education on birth weight differed for female and male infants, tending to be relatively unchanged for male infants and with mean birth weights increasing with maternal education in female infants. The effect of birth order differed by maternal age, with mean birth weight increasing with maternal age for first and second births; but being unaffected by maternal age for infants of birth order greater than two. We conclude that birth weight is influenced by common biological determinants across cultures, but is also influenced by social, ethnic, and environmental factors that are culture specific, of which some might be gender related.

Non-clinical safety evaluation of novel vaccines and adjuvants: new products, new strategies

Advances in molecular biology and biotechnology, coupled with an increased understanding of disease processes and mechanisms of protective immunity have facilitated the development of new rationally-designed vaccines utilising recombinant proteins, naked DNA, live vectors, genetically-modified toxins and whole dendritic and tumour cells for both prophylaxis and therapy of a wide range of indications. These new vaccine technologies coupled with novel adjuvants, delivery systems, formulations, dosing routes and regimes present many unique and difficult challenges in demonstrating product safety and efficacy to support clinical testing. This paper aims to review these novel vaccine and adjuvant technologies and to highlight the key safety issues potentially associated with them. Approaches taken to demonstrate vaccine safety by assessing systemic and local toxicity, biodistribution and persistence, immunogenicity and immunotoxicity, reproductive toxicology, safety pharmacology and genotoxicity within the current regulatory framework are presented.     

Toxicity of Citrate-Coated Silver Nanoparticles Differs According to Method of Suspension Preparation

To evaluate substance toxicity, it is critical to maintain specific concentrations of test substances throughout the exposure period. During the last decade, the need to improve methods for nanoparticle (NP) suspension preparations has gained attention because many published results on NPs toxicity have been inconsistent. Here, we compared the toxicity of citrate-coated silver nanoparticles (AgNPs) suspended by two different methods (fractionated vs. colloidal) in freshwater organisms (daphnia and medaka). Analytical methods (ICP-OES, DLS and UV absorbance) were employed to characterize behavior of AgNPs in suspension. Results showed that fractionated (stirred and settled) solution was less toxic to daphnia (13.8 µg/L) than colloidal solution (6.1 µg/L), suggesting that method of preparation was a critical factor that affected toxicity. However, differences in toxicity caused by suspension methods were not observed in medaka. Results indicate that the method used to prepare suspensions of NPs can affect toxicity, and that differences can exist among test organisms.     

Label-free,non-invasive,and repeatable cell viability bioassay using dynamic full-field optical coherence microscopy and supervised machine learning

We present a novel method that can assay cellular viability in real-time using supervised machine learning and intracellular dynamic activity data that is acquired in a label-free, non-invasive, and non-destructive manner. Cell viability can be an indicator for cytology, treatment, and diagnosis of diseases. We applied four supervised machine learning models on the observed data and compared the results with a trypan blue assay. The cell death assay performance by the four supervised models had a balanced accuracy of 93.92 ± 0.86%. Unlike staining techniques, where criteria for determining viability of cells is unclear, cell viability assessment using machine learning could be clearly quantified.